Bone development: The effect of short-term alpha-ketoglutarate administration on long-term mechanical properties of ribs in ram lambs

Tatara, Marcin R.; Tygesen, M. P.; Sawa-Wojtanowicz, B.; Krupski, Witold; Majcher, Piotr; Harrison, Adrian P.

doi:10.1016/j.smallrumres.2005.09.031

Cited by 27 publications

(25 citation statements)

References 8 publications

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“…This study shows that AKG treatment during neonatal development has a long‐term effect on the mechanical properties of ribs in pigs at slaughter. These results confirm the findings of a recent study of ribs in lambs (Tatara et al., 2007). However, rib bone density and the parameters from the weight carrying bones, such as humerus and femur were not generally affected at the time of slaughter.…”

Section: Discussionsupporting

confidence: 92%

“…Perhaps of most importance, for the current study, however is the fact that AKG treatment early in life, even with a fourfold lower dose than the study of Sawa-Wojtanowicz et al (2002), can have long-lasting effects on rib characteristics in growing pigs. Furthermore, the reported significant increase in mechanical parameters like ultimate strength, Younǵ s modulus and a tendency towards an increase in maximum elastic strength are in agreement with changes seen in the femur (Harrison et al, 2004) and ribs (Tatara et al, 2007) of lambs treated with 0.1 g/kg of b.w. per day AKG the first 14 days of life and slaughtered at day 130.…”

Section: Bone Geometry Morphology and Mechanicssupporting

confidence: 86%

“…Absorption is facilitated through secondary active transporters coupled to the sodium gradient known as the sodium dicarboxylate cotransporters (Pajor, 1999) with the highest rate of absorption in the small intestine followed by the stomach and colon (Buddington et al., 2004). Despite the low portal uptake of AKG and its short systemic half‐life (∼5 min) (Dabek et al., 2005), AKG increases bone mineral density and mechanical strength, when given orally to turkeys (Tatara et al., 2004, 2005a), pigs (Kowalik et al., 2005b) and lambs (Harrison et al., 2004; Tatara et al., 2007). Whilst the question of whether AKG supplements, given postnatally, have a permanent effect on bone mineralisation in pigs has yet to been resolved, a recent study has shown the potential usefulness of AKG treatment in preserving bone mass as well as lowering bone turnover in post‐menopausal women (Tocaj et al., 2003), results which suggest a link between enteral AKG and an increase in oestrogen levels.…”

Section: Introductionmentioning

confidence: 99%

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The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

Andersen

Tatara²,

Krupski

et al. 2008

Animal Physiology Nutrition

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The long-term effect of alpha-ketoglutarate (AKG) given for 21-24 days post-partum, on the skeleton of commercial pigs, was investigated. In experiment A, 12 pigs were given AKG [0.1 g/kg of body weight (b.w.) per day per os], while 12 controls were administered vehicle. At day 169, the left and right femur, humerus and sixth ribs were analysed for mechanical and geometrical properties and quantitative computed tomography. In experiment B, 32 piglets were divided equally into an AKG group (0.3 g/kg of b.w. per day) or a control group. Blood, taken at days 24 and 53 was analysed for plasma 17 beta-oestradiol. The main bone effect of AKG was to increase bone length in the sixth rib (7.3%, p < 0.01), ultimate strength (23%, p < 0.05), Young s modulus (52%, p < 0.001) and maximum elastic strength (31%, p = 0.056) compared with controls. In both experiments, AKG preferentially increased the growth of female piglets, whilst for male piglets AKG had the opposite effect. In addition, AKG elevated plasma 17 beta-oestradiol levels compared to those of controls at the end of the period of treatment (20%, p = 0.002). It is concluded that AKG has long-term effects on rib properties when given early in postnatal life whilst it elevates plasma 17 beta-oestradiol levels only so long as it is being administered.

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Section: Discussionsupporting

confidence: 92%

Section: Bone Geometry Morphology and Mechanicssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

Andersen

Tatara²,

Krupski

et al. 2008

Animal Physiology Nutrition

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“…In many tissues, including skeletal muscle, AKG is the carbon skeleton for the synthesis of Glu and Gln to improve protein status in animals (Hou et al, 2011;Hou et al, 2011;Hou et al, 2010;Blachier, Boutry, Bos, & Tome, 2009;Kristensen, Jungvid, Fernández, & Pierzynowski, 2002). Moreover, neonatal administration of AKG may be considered an effective factor in enhancing proper development and function of the skeleton during growth and later life (Tatara et al, 2007). AKG also promotes the growth of grass carp, broilers and weaned piglets, and improves their growth performance (Hu, Hou, & Ding, 2008).…”

mentioning

confidence: 99%

“…AKG has a long-term effect on skeletal development when given early in neonatal life and changes rib properties, which serves to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered an effective factor in enhancing proper development and function of the skeleton during growth and later life (Tatara et al, 2007). Based on the reported benefits of these studies, we hypothesized that AKG supplements have a positive effect on growth performance and N metabolism in piglets, and protein synthesis is enhanced by activating the mechanism of mTOR signalling, thereby increasing muscle mass and average daily gain (ADG).…”

mentioning

confidence: 99%

Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Zhao

Guo

Sun

2019

Animal Physiology Nutrition

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Excessive protein levels in diets result in incomplete digestion of nitrogenous nutrients that are excreted from the body, causing environment pollution. Alpha‐ketoglutarate (AKG) has been reported to decrease dietary protein levels, promote intestinal health in piglets and reduce environmental pollution. However, the underlying mechanisms of AKG are largely unknown. The objective of this study was to determine the effects of low‐protein diet supplementation of AKG on the growth performance, nitrogen metabolism, relative expression of amino acid transporter genes and mTOR signalling pathway of skeletal muscle in piglets. Forty‐eight piglets with an initial weight of 11.53 ± 0.04 kg were randomly divided into four groups. Each group had four replicates, and each replicate had three pigs. A low‐protein (LP) diet (crude protein was 14.96%) served as the control without AKG, while 0.5%, 1.0% and 1.5% AKG were added to the LP diet for the other experimental groups. The trial period lasted for 28 days. Compared with the LP group, the LP + 1.0%A and LP + 1.5%A groups increased the growth performance (p < .05);increased the mRNA levels of amino acid transporters in the duodenum, anterior jejunum and posterior jejunum (p < .05); and reduced faecal nitrogen and urine nitrogen emissions (p < .05). They also showed greater mRNA levels and phosphorylated protein levels for S6 kinase beta (S6K) (p < .05), mammalian target of rapamycin (mTOR) (p < .05) and 4E‐binding protein 1 (4EBP1) (p < .05) in skeletal muscle. An LP diet supplemented with AKG activated the mTOR signalling and promoted the ability of the small intestine to absorb protein, thereby increasing protein deposition. Taken together, an LP diet supplemented with AKG provides a theoretical basis for the promotion and application of AKG in piglet production.

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Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

Zdzisińska

Żurek

Kandefer‐Szerszeń

2016

Arch. Immunol. Ther. Exp.

163

133

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Alpha-ketoglutarate (AKG), an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. It functions as an energy donor, a precursor in the amino acid biosynthesis, a signalling molecule, as well as a regulator of epigenetic processes and cellular signalling via protein binding. AKG is an obligatory co-substrate for 2-oxoglutarate-dependent dioxygenases, which catalyse hydroxylation reactions on various types of substrates. It regulates the activity of prolyl-4 hydroxylase, which controls the biosynthesis of collagen, a component of bone tissue. AKG also affects the functioning of prolyl hydroxylases, which, in turn, influences the function of the hypoxia-inducible factor, an important transcription factor in cancer development and progression. Additionally, it affects the functioning of enzymes that influence epigenetic modifications of chromatin: ten–eleven translocation hydroxylases involved in DNA demethylation and the Jumonji C domain containing lysine demethylases, which are the major histone demethylases. Thus, it regulates gene expression. The metabolic and extrametabolic function of AKG in cells and the organism open many different fields for therapeutic interventions for treatment of diseases. This review presents the results of studies conducted with the use of AKG in states of protein deficiency and oxidative stress conditions. It also discusses current knowledge about AKG as an immunomodulatory agent and a bone anabolic factor. Additionally, the regulatory role of AKG and its structural analogues in carcinogenesis as well as the results of studies of AKG as an anticancer agent are discussed.

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Bone development: The effect of short-term alpha-ketoglutarate administration on long-term mechanical properties of ribs in ram lambs

Cited by 27 publications

References 8 publications

The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

The long‐term effect of α‐ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs

Effects of low‐protein diet supplementation with alpha‐ketoglutarate on growth performance, nitrogen metabolism and mTOR signalling pathway of skeletal muscle in piglets

Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

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